Time-resolved measurement is frequently conducted to obtain more information than continuous measurement for optically characterizing various samples. In time-resolved fluorescence spectroscopy, the fluorescence from a sample is measured as a function of time after illumination by a flash of light such as the output from a pulsed laser. Fluorescence lifetime of certain molecules is a sensitive reporter on local microenvironment which is generally independent of fluorophores concentration and can be used as a means of discriminating between molecules with spectrally overlapping emission.
Diffuse optical tomography (DOT) is an emerging technology that uses diffusive photons to measure the optical properties and their spatial distribution in thick biological samples. In time-domain DOT systems the intensity of diffusive photons is measured as a function of time, which is termed as temporal point spread function (TPSF). It has been well accepted that time-domain DOT can provide improved image quality than continuous wave (CW) DOT systems, in which the static state light signal is measured. Conventional time-domain DOT system employs either a streak camera or time-correlated single photon counting (TCSPC) to record the TPSF of diffuse photons. A streak camera has high time-resolution around 1 picosecond. However, it is limited by low dynamic range and temporal nonlinearity. Although TCSPC provides high sensitivity, high dynamic range, and time-resolution, its data acquisition speed is generally very slow as a large number of photons need to be collected one by one to reduce statistic errors. Recently, Mo et al (Fast time-domain diffuse optical tomography using pseudorandom bit sequences, Opt. Express Vol. 16, 13643-13650) disclosed a spread spectrum time-resolve measurement method that is much faster than TCSPC and more suitable for clinical applications. In a spread spectrum time-resolved DOT system, the laser output is modulated either directly or using an external modulator by a pseudo-random bit sequence (PRBS). The modulated beam is irradiated on a sample under investigation. The detected diffusive photon density at a given distance is a function of time, which equals the convolution of the PRBS with the TPSF. Cross-correlation between the PRBS and the detected signal yields an approximate measurement of the original TPSF at a specific time delay. Such an operation is implemented by the use of hardware devices such as a mixer and a low pass filter. A programmable delay line is used to shift the relative time delay between the PRBS and the detected signal so that the whole time spectrum is obtained point by point.
Image reconstruction in DOT is a process of generating maps of optical properties using the measured optical signals such as TPSFs. Usually it is computationally expensive if the TPSFs are directly used as input to the reconstruction algorithms due to the huge amount of measurement data. In practice, the TPSFs are pre-processed by using a variety of transforms to retrieve the essential information. The frequently used integral transforms include Laplace transform and Fourier transform. It has been demonstrated that Laplace transform with only a pair of transform parameters lead to uncompromised image quality (Zhang et al 2008, Three-dimensional scheme for time-domain fluorescence molecular tomography based on Laplace transforms with noise-robust factors, Opt. Express Vol. 16, 7214-7223). The advantages of using Laplace transformed data include simplified mathematical models, significantly reduced computation time, and low sensitivity to noises.